This study is a continuation of a multiphase study designed to evaluate the effectiveness and toxicity of whole body hyperthermia (WBH) in combination with chemotherapy in dogs with naturally occurring lymphosarcoma. Trials have been designed to test effectiveness of a single drug alone and combined with WBH before multiple drug combinations are initiated with WBH. Phase I and II studies to evaluate toxicity and effectiveness of doxorubicin alone or combined with WBH in dogs with canine lymphoma have been completed. A Phase III randomized study of similar mean and median remission times for drug plus WBH compared to drug alone. Development of drug resistant cell lines may have accounted for the failure to show an enhanced response. Cardiac toxicity is not statistically increased in the WBH + doxorubicin treatment group, however, the trend suggests enhanced toxicity in the dogs treated in this arm of the study. The proposed study will investigate a known heat and chemotherapeutic sensitizer, lonidamine (LON), with doxorubicin and WBH to determine if LON may further extend remission times. Phase I studies on LON in normal dogs have been completed. In addition, doxorubicin + lonidamine plus minus WBH studies to evaluate changes in doxorubicin-induced cardiac toxicity are near completion. Since doxorubicin-induced cardiotoxicity is a clinically significant problem that may be enhanced when the drug is administered at elevated temperatures, a much less cardiotoxic drug, mitoxantrone (MX) will be evaluated. Heat sensitization by mitoxantrone is known to occur within the temperature range obtainable with WBH. Potential doubling time and growth fraction will be evaluated, using flow cytometry, to determine predictive value.